Epithelial ovarian cancer is the most lethal of the female genital tract cancers. The majority of early-stage cancers are asymptomatic, and over three-quarters of the diagnoses are usually made at a time when the disease is often incurable because regional or distant metastasis has already been established (Wingo et al, 1998). Owing to paucity of symptoms and their insidious onset, most patients present with advanced disease with five-year survival rates being a mere 30% (Kristensen et al, 1997).
Regular pelvic examinations and CA-125 biomarker measurements followed by radiological diagnosis on an individualized basis have been the current practice for detection of this enigmatic condition. Although current early detection protocols have generally involved a combination of ultrasound and serum CA-125 levels, these protocols have met with limited success (Karlan et al., 1999). The largest randomized screening trial to date, which evaluated more than 20,000 women indicated a survival benefit, however, this did not translate into fewer deaths between the screened and unscreened groups of women (Jacobs et al., 1999).
Moreover, CA-125 concentrations are elevated in women with benign gynaecologic conditions including ovarian cysts, endometriosis and uterine fibroids which form part of the differential diagnosis for ovarian cancer (Mackey et al., 1995). Also, women with hepatic disease, renal failure, pancreatitis and other conditions may have elevated CA-125, thus limiting the role of this protein as a marker for ovarian cancer (Devarbhavi et al., 2002). Screening with additional serum markers including CA-19-9 and lysophosphatidic acid as adjuncts to CA-125 screening has also not been shown to be clinically relevant for diagnostic purposes (Woolas et al., 1999).
Most women with ovarian cancers are asymptomatic during the early stages of this disease, and most women present in FIGO (International Federation of Gynecology and Obstetrics) stages III and IV. The currently accepted management for advanced stage ovarian cancer is primary debulking surgery in order to achieve an optimal cytoreduction (defined as residual tumour less than 2 cm) followed by chemotherapy. The surgery usually involves total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and pelvic and para-aortic lymphadenectomy. Despite cytoreductive surgery, morbidity and mortality rates remain high with minimal impact on survival rates (Michel et al., 1997; Vergote et al., 1998). In contrast, early stage disease is associated with up to 95% survival (Cannistra, 2004) and a fertility sparing surgical approach can be used in patients who desire fertility preservation (Robinson et al., 1992).
Advances in laparoscopy have allowed gynecologists to perform procedures previously accomplished only by laparotomy. Currently gynecologists perform laparoscopic procedures for treatment of benign ovarian cysts and occasionally encounter unexpected malignancies (Maiman et al., 1991). Inappropriate surgery due to missed diagnosis is associated with poor patient outcome. It is therefore important that an accurate intra-operative diagnosis of malignancy is made for appropriate surgical and therapeutic intervention.
The current state-of-the-art for intraoperative diagnosis is frozen section biopsy (Yeo et al., 1998). This is an expensive, resource and labour intensive test that is not available in many hospitals around the world, and even where available is usually a limited service during office hours. Its accuracy has been quoted from 100% (Lim et al, 1997) to a low of 88.7% (Canis et al., 2004). A reliable, cheaper and more readily available alternative that could be made available to most hospitals is needed.
As such, a method that solves or at least alleviates the problems and limitations of the prior art will be welcome.